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Common variation in the MOG gene influences transcript splicing in humans

journal contribution
posted on 2023-05-17, 04:43 authored by Jensen, CJ, Jim Stankovich, Butzkueven, H, Oldfield, BJ, Rubio, JP
Multiple sclerosis (MS) is a complex autoimmune disease characterised by demyelinating lesions in the central nervous system (CNS) and myelin oligodendrocyte glycoprotein (MOG), a CNS-restricted protein expressed on the outer cell membrane of oligodendrocytes, has been linked with disease pathogenesis. We have investigated whether expression of MOG in post-mortem human brain tissue is associated with genetic variations in the MOG gene that have previously been associated with genetic susceptibility to MS (520GNA, rs3130253, V145I and 511GNC, rs2857766, V142L). Using quantitative reverse transcriptase PCR (qPCR), we found that the haplotype containing the 520A (rs3130253A, I145) allele is associated with a 1.7-fold increase in splicing of exon 2 to exon 3, which encodes the extracellular and transmembrane domains of MOG. Using predictive algorithms, we found that the 520GNA variant also alters a putative exonic splicing enhancer (ESE) involving the SC35 and SRp55 RNA-binding proteins, supporting the notion that this variation has a regulatory effect. No consistent differences in allele-specific expression were observed for any of the SNPs using the SNaPshot® method. In this exploratory study we have observed that changes in splicing, but not expression levels, are associated with common genetic variation in the MOG gene. Further work is now required to confirm these data and determine whether this altered MOG expression profile, which is predicted to be over-represented in Northern Europeans with MS, is relevant to the pathophysiology of this debilitating disease.

History

Publication title

Journal of Neuroimmunology

Volume

229

Issue

1-2

Pagination

225-231

ISSN

0165-5728

Department/School

Menzies Institute for Medical Research

Publisher

Elsevier Science Bv

Place of publication

Po Box 211, Amsterdam, Netherlands, 1000 Ae

Rights statement

The definitive version is available at http://www.sciencedirect.com

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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